Wanstall Janet C, Gambino Agatha, Jeffery Trina K, Cahill Marian M, Bellomo Daniela, Hayward Nicholas K, Kay Graham F
School of Biomedical Sciences, Department of Physiology and Pharmacology, University of Queensland, St. Lucia, Qld. 4072, Brisbane, Australia.
Cardiovasc Res. 2002 Aug 1;55(2):361-8. doi: 10.1016/s0008-6363(02)00440-6.
To test the hypothesis that Vegf-B contributes to the pulmonary vascular remodelling, and the associated pulmonary hypertension, induced by exposure of mice to chronic hypoxia.
Right ventricular systolic pressure, the ratio of right ventricle/[left ventricle+septum] (RV/[LV+S]) and the thickness of the media (relative to vessel diameter) of intralobar pulmonary arteries (o.d. 50-150 and 151-420 microm) were determined in Vegfb knockout mice (Vegfb(-/-); n=17) and corresponding wild-type mice (Vegfb(+/+); n=17) exposed to chronic hypoxia (10% oxygen) or housed in room air (normoxia) for 4 weeks.
In Vegfb(+/+) mice hypoxia caused (i) pulmonary hypertension (a 70% increase in right ventricular systolic pressure compared with normoxic Vegfb(+/+) mice; P<0.001), (ii) right ventricular hypertrophy (a 66% increase in RV/[LV+S]; P<0.001) and (iii) pulmonary vascular remodelling (a 27-36% increase in pulmonary arterial medial thickness; P<0.05). In contrast, in Vegfb(-/-) mice hypoxia did not cause any increase in either right ventricular systolic pressure or pulmonary arterial medial thickness; also right ventricular hypertrophy (41% increase in RV/[LV+S]; P<0.001) was less pronounced (P<0.05) than in Vegfb(+/+) mice.
Vegf-B may have a role in the development of chronic hypoxic pulmonary hypertension in mice by contributing to pulmonary vascular remodelling. If so, the effect of Vegf-B appears to be different from that of Vegf-A which is reported to protect against, rather than contribute to, hypoxia-induced pulmonary vascular remodelling.
验证血管内皮生长因子B（Vegf - B）促成小鼠因长期缺氧所致肺血管重塑及相关肺动脉高压这一假说。
测定Vegfb基因敲除小鼠（Vegfb(-/-)；n = 17）和相应野生型小鼠（Vegfb(+/+)；n = 17）的右心室收缩压、右心室/[左心室+室间隔]比值（RV/[LV+S]）以及叶内肺动脉（外径50 - 150微米和151 - 420微米）中膜厚度（相对于血管直径），这些小鼠分别暴露于慢性低氧环境（10%氧气）或饲养于常氧环境（正常空气）4周。
在Vegfb(+/+)小鼠中，缺氧导致（i）肺动脉高压（与常氧Vegfb(+/+)小鼠相比，右心室收缩压增加70%；P<0.001），（ii）右心室肥厚（RV/[LV+S]增加66%；P<0.001），以及（iii）肺血管重塑（肺动脉中膜厚度增加27 - 36%；P<0.05）。相比之下，在Vegfb(-/-)小鼠中，缺氧未导致右心室收缩压或肺动脉中膜厚度增加；右心室肥厚（RV/[LV+S]增加41%；P<0.001）也不如Vegfb(+/+)小鼠明显（P<0.05）。
Vegf - B可能通过促成肺血管重塑在小鼠慢性低氧性肺动脉高压的发展中起作用。如果是这样，Vegf - B的作用似乎与Vegf - A不同，据报道Vegf - A可防止而非促成缺氧诱导的肺血管重塑。
